dos_Jan_2007

of some researchers is that if the transplant produces a 2- Š Ability to move in space as with a healthy human eye
dimensional pattern of electrical signals in response to Š Must e simple to implant
light, e.g. in the shape of an alphabetical character projected
onto the transplant, the underlying retina which is not Š Mustbe easy to deal with by the patient
light-responsive will still be able to pick up the signal
pattern from the transplant and transmit it to the brain. Š Good technical support as well as ongoing training of
ophthalmic surgeons responsible for implanting .
In order for a retinal transplant to work, several
technologies have to be developed: Outlook and Perspectives

1. The cells in the transplant must stay alive for a long The last 10 years of visual prosthesis research has
time, preferably for the life of the recipient demonstrated that the interdisciplinary approach of
combining engineering and medical know-how has an
2. Those cells must have, and maintain, the light-sensing important contribution to make in a field where no
activities of normal, healthy retina cells treatment is available for blind patients. Several research
groups have developed prototypes for retinal implants
3. Those cells must transmit electric or electrochemical which will be evaluated in terms of safety and efficacy.
signals to the brain, which the brain can interpret as The quality of vision or visual acuity or visual field
the experience of vision. properties will depend on a number of factors of the
individual patient and not only of the technical implant.
The other area of investigation is development of a However, even if these implants will restore only minor
cortical implant for patients who would not benefit from a visual functions.But in person with bare light
retinal implant. Such patients include those who have lost perception,improvement to 20/400 vision could offer the
vision due to a number of conditions, including glaucoma, means of getting around in unfamiliar places,recognizing
diabetic retinopathy or trauma to the eye. This prosthetic human figures and accessing the public transportation.
device will be implanted in the visual cortex of the brain,
where sight is interpreted. It, too, will be an extraordinarily A large number of open questions remain, the most
tiny device with its own microcomputer. With a cortical important being the long-term stability and function of
implant, information from a tiny digital camera possibly such a device, the biological behavior of the interface
mounted on glasses, could be transmitted to electrodes between the electrodes and the target tissue, and the target
implanted in the visual cortex, bypassing the non-working tissue itself. At present it is not known how in the retina
retina or optic nerve. such a coupling between a technical device and the retina
itself will function over many years. These questions can
There is research to support this concept. Blind only be answered by long term human clinical trials.
individuals who have received experimental stimulation
of the visual cortex with electrodes have experienced Retinal implants are showing promise as replacements
localized images of light called “phosphenes.” There is some for diseased photoreceptor cells, but the work is still in the
evidence that the brain can learn to relate these different earliest stages of experimentation and the results are still
neural signal to previously learned physical and mental primitive, allowing the subject to see only areas of light
knowledge of the world. This would be similar to cochlear and dark at this time. Still, the progress being made is
implants in the ear for the hearing impaired. These require significant, and probably the best hope so far of restoring
a learning process for effective use. at least a semblance of sight to the blind.

While the cortical implant has the potential to help References
greater numbers of people than the retinal implant, it may
require a longer investigation period since it involves 1. Krumpaszky HG, Klauss V. Epidemiology of blindness and eye
implanting a device in the brain and because it has not disease. Ophthalmologica 1996; 210: 1-84.
been studied as much as the retinal implant. Both the
retinal and cortical implants represent immense biological 2. William LL, Shannon BT, Chambers RB, et al. systemic
and technological challenges. While the substances used immunostimulation after retinal laser treatment in retinitis
for both implants should be inert, meaning that they cannot pigmentosa. Clin Immunol Immunopathol 1992; 64: 78-83.
be absorbed into the body, extensive testing will be
necessary during and after their fabrication to make sure 3. Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of
that they are safe and effective.26,27 vitamin A and vitamin E supplementation for retinitis pigmentosa.
Arch Ophthamol 1993; 111: 761-772.
Properties of ideal Retinal Implant
4. Skogstad M, Bast-Pattersen R, Tynes T, et al. Treatment with
Š Fully working implant hyperbaric oxygen. Illustrated by the treatment of a patient with
Š Long-term biocompatiility retinitis pigmentosa. Tidsskr Nor Laegeforen 1994; 114: 2480-
2483.
Š Acceptable degree of improvement of ability to see
5. Berson EL, Juancho F, Remulla C, et al. Evaluation of patients with
retinitis pigmentosa receiving electric stimulation, ozonated blood,
and ocular surgery in Cuba. Arch Ophthalmol 1996; 114: 560-563.

6. Pelaez O. Evaluation of patients with retinitis pigmentosa receiving
electric stimulation, ozonated blood, and ocular surgery in Cuba.

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Arch Ophthalmol 1997; 115: 133-134. image sensors.Bruges Workshop Proceedings.1997.IEEE
Piscataway
7. Ali RA, Reichel MB, Trasher AJ, et al. Gene transfer into the mouse 18. Eckmiller R.Retina implants with adaptive retina encoders,RESNA
Research Symposium.1996.pp21-24.
retina by an adeno associated viral vector. Hum Mol Genet 1996; 19. Eckmiller R.Learning retina implants with epiretinal
contacts.Ophthalmic Res .1997.29:281-289.
5: 591-594. 20. Berk H,Held S,Alteheld N,et al.Explantation of tack fixated epiretinal
microcontact foils in rabbits-preliminary observations.ARVO
8. Kohn DB, Sadelain M, Glorioso JC. Occurrence of leukemia Abstract 2002:4456.
21. Celeste Biever.Solar-Powered Retinal Implants.New Scientist
following gene therapy of X-linked SCID. Nat Rev Cancer 2003; Magazine.April 2006.
22. Alteheld N, Vobig MA, Bajwa R, et al. Biocompatibility tests on
3: 477-488. the intraocular vision aid IOVA. Biomed Tech (Berl) 2002; 1: 176-
178.
9. Brindley GS. Sensations produced by electrical stimulation of the 23. WWW.Nature.com/news/2005
24. Humayun MS, de Jaun E, Dagnelie G, et al. visual perception
occipital poles of the cerebral hemispheres, and there use in elicited by electrical stimulation of retina in blind subjects. Arch
Ophthalmol 1996; 114: 40-46.
constructing visual prosthesis. Ann R Coll Surg Engl 1970; 47: 25. Chow AY, Packo KH, Pollack JS, et al. Subretinal artificial silicon
retina microchip implantation in retinitis pigmentosa patients: long
106-108. term follow-up. ARVO Abstact 2003: 4205.
26. Eysel UT,Walter P,Gekaler F,et al.Optical imaging reveals 2-
10. Brindley GS, Lewin WS. The sensations produced by electrical dimensional patterns of cortical activation after locak retinal
stimulation with sub and epiretinal visual prosthesis.ARVO
stimulation of the visual cortex. J Physiol 1968; 196: 479-493. Abstract.2002.4486.
27. Schanze T,Wilms M, Eger M,et al.Activation zones in cat visual
11. Peyman G,Chow Ay,Liang C,et al.Subretinal semiconductor cortex evoked by electrical retinal stimulation.Graefes Arch Clin
Exp Ophthalmol.2002.240:947-954.
microphotodiode array.Ophthalmic Surg Lasers 1998.29:234-241. 28. Rizzo JF 3rd, Wyatt J, Humayun M, et al. Methods and perceptual
thresholds for short term electrical stimulation of human retina
12. Zrenner E,Stett A,Weiss S.Can subretinal microphotodiodes with microelectrode arrays. Invest Ophthalmol Vis Sci 2003; 44:
5355-5361.
successfully replace degenerated photoreceptors?Vision

Res.1999.39:2555-2567.

13. Schwahn HN,Gekeler F,Kohler K,et al.Styudies on feasibilty of a

subretinal visual prosthesis:data from Yucatan micropig and

rabbit.Graefes Arch Clin Exp Ophthalmol.2002.239:961-967.

14. Eckmiller R.Towards retina implants for improvement of vision in

human with RP-challenges and first results,1995.vol .1.Proc

WCNN,INNS Press,Lawrence Erlbaum

Associates,Hillsdale,pp228-233

15. Humayun M, Greenberg RJ, Mech BV, et al. Chronically implanted

intraocular retinal prosthesis in two blind subjects. ARVO Abstract

2003:4206.

16. Rizzo JF 3rd,Wyatt J,Humayun M,et al.Retinal prosthesis:an

encouraging first decade with major challenges ahead.

Ophthalmology 2001.108:13-14.

17. Huppertz J,Hausschild R,Hosticka BJ,et al.Fast CMOS imaging

with high dynamic range.In:Charge Coupled devices and advanced

January, 2007 52 DOS Times - Vol. 12, No. 7

HARDWAREHINTS

Rebound Tonometry

Jatinder Bali MS, Yogesh K Gupta MD

The first prototypes of a rebound type tonometer were The rebound tonometer consists of a pair of coils
developed by Antti Kontiola in 1994. Antti Kontiola's coaxial with the probe shaft that are used to propel the
original idea was to "develop a device that would enable lightweight magnetized probe toward the cornea and to
IOP monitoring with special patient groups, such as sense its movement. Appropriate electronic components
children and demented patients, whose monitoring with allow for the probe movement to be initiated by the
existing instruments was nearly impossible" e.g. due to solenoid coil and monitored by the sensing coil.
the requirement for absolute immobility. topical anesthetic
use hampered monitoring significantly and limited the An applied pulse of electrical current induces a
task to doctors only. magnetic field within the solenoid, causing the probe to be
propelled onto the cornea from where it rebounds. Motion
In this concept, an ultra-light probe is made to collide parameters of the probe can be determined from movement
at a very low speed with the surface of the cornea. At this of the magnetic probe, which generates a voltage in the
moment the device records the deceleration and motion of sensing coil that is readily recorded and analyzed.
the probe during rebound in a time frame of a few
microseconds very accurately. The voltage is proportional to the magnetic field
induced, which is proportional to the probe speed. Several
In 1994-95 the first measurements were performed motion parameters of the probe can be extracted from the
after the prototype was developed. Between 1998 and 2001 sensing coil oscilloscope record and related to the IOP, such
a joint development project with a university reseach as the time of eye contact, the velocity of return, and the
center in New York, USA was followed by clinical tests. deceleration time. The inverse of deceleration time
(deceleration time-1) parameter is most closely correlated
In July, 2003 CE approval was granted to the to IOP.
commercial product and iCare® rebound tonometer for
human medical use was launched. It did not require the The probe consists of a magnetized steel wire shaft
use of topical anesthetic. with a round plastic tip (1 mm diameter) at its front end.
This round tip minimizes the possibility of corneal damage
The device: from probe impact. Although generally more accurate,
lighter probes are more prone to influence by external
Tiolat's iCare® tonometer is a cell-phone sized, unrelated magnetic fields, which makes their behavior less
lightweight, portable, battery operated instrument. The predictable.
measuring probe touches the eye so gently that it is barely
perceptible. No topical anesthetic is required, making the For measurements the speed before impact is
iCare® even suitable for self-monitoring IOP at home. The approximately 0.2 m/sec. The deceleration varies depending
instrument is designed to take and calculate the average of on the eye pressure.
six measurements. Each measurement is taken in a fraction
of a second. This reduces the influence of factors outside of Caliberation
the eye. The TonoLab is based on the newly patented
induction-based-rebound-method which allows Device calibration was done on enucleated eyes which
intraocular pressure (IOP) to be measured accurately, were cannulated with a 26-gauge needle at 90° to the
rapidly, and without using a local anesthetic. This visual axis with the aid of an operating microscope.
handheld mobile tonometer has the latest IOP Cyanoacrylate glue was used around the point of entry of
measurement technology for the screening of glaucoma. It the needle in the anterior chamber to prevent leakage of
has a new probe technology that prevents cross aqueous humor. IOP was controlled by adjusting the height
contamination. There is no risk of microbial contamination, of a variable column of balanced salt solution (BSS) attached
as one-use probes are used in the measurement. The to the cannula (open-stopcock method). IOP was verified
screening is fast, effective and reliable. and continuously recorded by a pressure transducer
(Model TNF-R; Ohmeda, Louisville, CO) connected to the
Hindu Rao Hospital, cannula, which was calibrated before eye cannulation by
Bara Hindu Rao, varying the height of the BSS column.
Delhi
The starting distance of the probe from the corneal
surface was approximately 2.4 mm. Only measurements
that occurred within a narrow time window (5 ms) 12 ms

DOS Times - Vol. 12, No. 7 53 January, 2007

subsequent to triggering A rebound tonometer
the tonometer probe were device for mouse IOP
accepted for analysis. measurement was adapted
from different prototypes.
The ratio of probe The developed prototype
speed immediately before was more accurate than
impact over the the TonoPen in measuring
deceleration during impact the IOP of rats. In addition,
with the cornea was the goal of measuring IOP
related to manometric from the mouse eye was
(true) IOP. The method was successful and the
based on impacting a very prototype was able to
light probe to the eye at the measure IOP accurately in
very low speed (11-13mg, vitro and in vivo.
0.1-0.2m/s) and measuring
the motion parameters of A commercial version of
the probe during collision the rebound tonometer is
to the eye (deceleration, impact time, etc,). The movement now available. It allows rapid IOP measurements instantly
energy of the probe was very small (less than 0.25 J) and displayed in mm of mercury. The tonometer requires no
most of that was rebounded (not absorbed by the eye) so calibration and features species-specific modes also. The
there was no damage to the eye. Several measurements risk of microbiological cross contamination has been
could be made over a long period of time. It is closely eliminated with a single use probe. The time needed from
related to the principle of vibration tonometry and the induction to the results of dependable consistent readings
earlier Krakau tonometer. It has been applied recently for is minimal. However, today it is still more of a research
measuring IOP in large animal eyes ex vivo and clinically tool than an office one. But the advantages offered by the
in humans. technique make it an appropriate one for large-scale
exploitation in office practice. The rebound tonometer
The advantages of iCare® over existing instruments readings have been reported to correlate well with
goldmann applanation tonometer (GAT) in recent studies.
are its handy size, true portability (no power cords), It has been found to be more accurate than the tonopen.
Coupled with the advantage of minimal contact and
patient and user-friendliness, and its accuracy. Measuring avoidance of anaesthetic use it may be an extremely useful
instrument in clinical practice. It can be used in children
also does not require the use of topical anesthetics. Corneal and even restless patients, as the instrument does not
require absolute stillness as for the previous techniques.
thickness and hydration is expected to affect the I/I method
References:
of tonometry as it affects most of the other methods
1. Danias J, Kontiola Al, Fillppopoulos
(applanation, Mackay-Marg tonometry, T, Mittage T. Method for the non-
invasive measurement of intraocular
pneumatonometry). pressure (IOP) in mice. Invest
Ophthalmol Vis Sci 2003;44:1138-
Use of a mouse model for studies of glaucoma was more 1141
2. KontiolaAl, Goldblum D, Mittag T,
preferable in this calibration as it was easier and more Danias J.The Induction/Impact
Tonometer: A New Instrument to
economical to maintain Measure IOP in the Rat. Exp.Eye Res
2001;73:781-785
mice than larger animals. 3. Goldblum D, Kontiola A, Danias J,
Chen B, Mittag T.Noninvasive
Mice have similar eye determination of intraocular pressure in
the rat eye.Comparison of an electronic
physiology when tonometer (TonoPen), and a rebound
(impact probe) tonometer.GraefesArch
compared to human eyes. Clin Exp Ophthalmol 2002;240:942-
946
However, the front 4. Wan-Heng Wang, J. Cameron Millar,
Iok-Hou Pang, Martin B Wax,Abbot F.
chamber of a mouse eye Clark.Noninvasive Measurement of
Rodent Intraocular Pressure with a
contains only 2-4 l Rebound Tonometer.IOVS 2005;
46(12):746-48
aqueous, making it a

challenge to measure IOP.

First measurements
were made in 1997 by
cannulating the eye of an
anesthetized mouse with
a very small needle. This
method required very
deep anesthesia, which in
turn, lowered the IOP.

January, 2007 54 DOS Times - Vol. 12, No. 7

HARDWAREHINTS

Pascal® Dynamic Contour Tonometry

Ruchi Goel MS, DNB, FICS, Usha Yadava MD, DNB, Navjot Kaur MBBS

Glaucoma is characterized by progressive atrophy of thickness due to edema causes underestimation of lOP
the optic nerve head leading to irreversible loss of vision. whereas in normal corneas, higher pressures are obtained
Measurement of precise intraocular pressure (lOP) is in thicker corneas and lower pressures are obtained in
important for work-up of any glaucoma patient. All the thinner corneas.
clinical tonometers measure the lOP by relating a
deformation of the globe to the force responsible for Ehlers1 et al published a table in which the average
deformation. error is 0.7mm of Hg for 10μ of deviation from the mean of
520μ.
The two basic tonometers are the indentation and
applanation tonometers. The shape of deformation by Tonopen is a hand-held Mackay-Marg type tonometer
indentation tonometer is a truncated cone. It displaces a which has a strain gauge that creates an electrical signal
large volume of intraocular fluid and measurements are as the footplate flattens the cornea. A built-in single chip
influenced by ocular rigidity, blood volume alterations, microprocessor senses the proper force curves and
corneal biomechanics and Moses effect. averages 4-10 readings to give a final digital readout.

Applanation tonometer produce a simple flattening. It Even the Tonopen has shown to be influenced by CCT
measures the force required to applanate a standard area with errors of 0.29mm of Hg per 10μ in men and 0.12mm of
of corneal surface. The prototype is Goldmann applanation Hg per 10μ in women2.
tonometer (GAT) which was introduced in 1954.
In LASIK patients besides alteration of corneal
The Goldmann applanation tonometer (GAT) is based thickness, there is alteration of corneal rigidity. Patel and
on the Imbert Fick law which states that an external force Aslanides proposed that the increase in proteoglycans and
(F) against a sphere equals the pressure in the sphere ( P) hyaluronic acid that occurs after excimer laser
times the area flattened (applanated) by the external force photoablation causes accumulation of water in stroma
(A) (Fig.1). which affects corneal rigidity which leads to
underestimation of lOP3. The association between myopia
F=PxA and chronic open angle glaucoma has been supported by
The validity of the law requires that the sphere be large population based surveys4,5.
perfectly spherical, dry, flexible and infinitely thin.
The mathematical calculations are based on the By underestimating lOP in post refractive surgery
presumed average central corneal thickness. Corneal patients one can miss out on potential glaucoma suspects.

F Corneal curvature has also been shown to influence
lOP measurements by GAT. There is increase in lOP by
A 1mm Hg for every 3D increase in corneal power6.

P Irregular corneas distorts the semicircles and interferes
with the accuracy of lOP estimates7.
Fig.1: Principle of Applanation Tonometry.
To circumvent the systematic errors introduced in
Guru Nanak Eye Centre, ‘non-standard eyes’ the concept of dynamic contour
Maulana Azad Medical College, New Delhi tonometry (OCT) has come up. PASCAL® Dynamic contour
tonometer, engineered and manufactured by SMT Swiss
Ophthalmic Systems Group Company is marketed by
Ziemer Ophthalmic Systems.

The PASCAL® DCT is a digital tonometer that provides
direct transcorneal measurement of intraocular pressure
and is sensitive enough to detect the ocular pulse amplitude
(OPA) due to the patient’s heart beat.

PASCAL® DCT is slit lamp mounted (Fig.2). It is a
contour tonometry. It makes use of pressure sensors which
are accurate and stable devices for measuring the lOP non-
invasively. The contour matched tonometer tip has a
concave surface which allows the cornea to assume the

DOS Times - Vol. 12, No. 7 55 January, 2007

PRESSURE SENSOR Hg, but often upto 9 mmHg). From static
lOP measurement, it is not possible to
know exactly on pulse pressure curve
as to when the measurement was taken.

Pascal records the inter pressure
curve with a time resolution of 100 data
points per second hence captures the full
dynamics of lOP (Fig.6). There is a
positive correlation between lOP and
OP A and negative correlation with
Axial length.

Fig. 2: Slit Lamp mounted Pascal Fig.3: Principle of Contour tonometry. Siganos et al compared PDCT with
OCT. Non contact tonometer(NCT) and GAT.
They found that NCT is fairly accurate
Fig.4: Disposable tip. Fig.5: LCD in ‘normal’ range of lOP, less accurate in
eyes with high lOP and poor fixation. In
shape which it naturally takes up when pressure on both contrast to PDCT, GAT and NCT tended
sides of the cornea are equal and hence no net bending to underestimate lOP in all patients
forces are acting on the cornea (Fig. 3). after LASIK. This could be caused not
only by the change in corneal thickness,
Contour matching is independent of contact diameter but most likely by a change in corneal
and appositional force. It converts the detected pressure rigidity after LASIK. A decrease in
digitally into a numeric result with 12-bit (1/1000mmHg) corneal rigidity would facilitate corneal
numerical precision. The results are free from operator bias. applanation and explain in part, the
drop in GAT and NCT readings after LASIK8.
It is easier and faster than conventional tonometers.
There is no need for additional pachymetry and conversion In conclusion, Pascal tonometry is a precise, contour,
of the tonometer estimate. and dynamic tonometry which has been introduced with
the idea to overcome the factors related to corneal thickness
and biomechanics.

More clinical documentation is required for assessing
its actual usefulness in diagnosis and follow up of glaucoma
patients.

References:

Pascal sensor cap disposable tip covers are convenient 1. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central
corneal thickness. Acta Ophthalmol 1975; 53: 34.
and easy to use (Fig 4). The tip is touched on the eye for a
2. Dohadwala AA, Munger R, Damji KF. Positive correlation
few seconds, the result is read from illuminated between Tonopen intraocular pressure and cenral corneal

LCD.(Fig.5). thickness. Ophthalmology 1998; 105: 1849.

Ocular haemodynamics causes lOP to fluctuate, at the 3. Patel S, Aslanides IM. Main causes of reduced intraocular pressure
after excimer laser photorefractive keratectomy( letter). J Refract
patient’s cardiac rate, by several mmHg (typically 3mm of surg 1996; 12:673.

4. Weih LM et al. Prevalence and predictors of the open angle
glaucoma: results from the visual impairment project.
Ophthalmology 2001; 108: 1966

5. Wong Ty et al. Refractive errors, intraocular pressure and glaucoma
in a white population . Ophthalmology 1999; 106: 2010

6. Mark HH. Corneal curvature in applanation tonometry. Am J
Ophthalmol 1973;76:223

7. Moses RA. The Goldmann applanation tonometer. Am J Ophthalmol
1958; 46: 65.

Fig.6: Ocular pulse amplitude 8. Siganos OS, Papastergiou GI, Moedas C. Assessment of the Pascal
dynamic contour tonometer in monitoring intraocular pressure in
unoperated eyes and eyes after LASIK. J Cataract Refract Surg
2004; 30: 746-751.

January, 2007 56 DOS Times - Vol. 12, No. 7